Stem Cell Image of the Week: This week’s image shows dopamine producing brain cells. These are the cells that are depleted in people with Parkinson’s Disease.
Photo courtesy of B. Bick, . Poindexter, UT Med. School/SPL
Parkinson’s disease news: a new clinical trial, a new face of the disease (Kevin McCormack)
In his long and illustrious career Alan Alda has worn many hats. First as the star of the hit TV show “M*A*S*H” (the season finale of that is still the most watched TV show ever), then as a writer, director and movie star and, more recently, as the face of popular science and science communications. This week Alda revealed that he has Parkinson’s disease (PD).
In a post on Twitter he said:
“I have decided to let people know I have Parkinson’s to encourage others to take action. I was Diagnosed 3 and a half years ago, but my life is full. I act, I give talks, I do my podcast, which I love. If you get a diagnosis, keep moving!”
CIRM Board member David Higgins echoed those sentiments in an interview on KUSI TV News, San Diego. Dr. Higgins is the patient advocate member for Parkinson’s on the Board, and was diagnosed with PD in 2011, he says being active physically and intellectually are important in helping cope with PD and leading a normal life.
There was also some encouraging news about PD on the research front. Scientists in Japan are about to start a clinical trial using iPSCs to treat people with PD. The cells are created by taking blood stem cells from healthy donors and turning them into dopaminergic progenitors, precursors to the kind of cell destroyed by PD. The cells will then be transplanted into the brains of seven patients with PD.
The researchers, from Kyoto University, say previous studies show the cells could survive in monkeys for up to two years and help improve symptoms of Parkinson’s disease in the primates.
New Molecular Probe Targets Elusive Cancer St
em Cells in Mice (Adonica Shaw)
A group of researchers at the University of Illinois made an advance in how we treat cancer patients this week. In a paper, published in the journal ACS Central Science, the researchers described a new and more effective way of identifying cancer stem cells in cultures of multiple human cancer cell lines as well as in live mice.
After a primary tumor is treated, cancer stem cells may still lurk in the body, ready to metastasize and cause a recurrence of the cancer in a form that’s more aggressive and resistant to treatment. The researchers developed a molecular probe that seeks out these elusive cells and lights them up so they can be identified, tracked and studied not only in cell cultures, but in their native environment: the body.
While other commercial agents are available to flag cancer stem cells, their application is limited, Chan said. Some cannot distinguish between live and dead cells, others can mistakenly bind to wrong targets. The most popular – antibodies that seek out markers on the cell’s surface – are specific to cell types and their large size can prevent them from reaching the small spaces where cancer stem cells tend to lurk. All are designed for use in cell cultures or artificial tumor environments, which lack the complexity of the whole body, Chan said.
In contrast, their new probe, called AlDeSense, is a small molecule that binds to an enzyme related to the property of stemness in cancer cells. The probe becomes activated, emitting a fluorescent signal only when it reacts with the target enzyme – which cancer stem cells produce in high concentrations.
In a series of experiments, the group found that the enzyme seems to be a marker of stemness across many types of cancer, indicating that AlDeSense may be broadly applicable for clinical imaging.
The researchers demonstrated that AlDeSense is compatible with two major cellular techniques – flow cytometry and confocal imaging.
The ability to find and track cancer stem cells in the body, as well as their state of stemness – the signal decreases as the cells differentiate – allowed the researchers to follow cells from injection to tumor as they spread through the bodies of the mice, answering some fundamental questions of how cancer stem cells behave.
According to the researchers nobody knew what happens between injection of cancer stem cells and removal of a tumor prior to this study. There are a lot of models that hypothesize about how cancer stem cells differentiate and grow, but limited experimental data exists.
Through their study, they saw the stemness properties are maintained in the population, even after they metastasize. There’s something about the environment in the body that supports stem cell characteristics. With AlDeSense, now they can profile that environment.
Since they know that the probe only interacts with that one target, they can use the probe to look for a drug that can inhibit this enzyme and verify it in cells and in live animals. The group is currently pursuing a screening for inhibitors or drugs that can kill cancer stem cells by targeting this enzyme.
Tackling a Rare Brain Disease May Also Lead to Alzheimer’s Insights (Todd Dubnicoff)
Alzheimer’s disease and ALS are very complex neurodegenerative disorders, making it very difficult for researchers to tease out the underlying causes let alone find treatments. To make inroads into a better understanding of these incurable diseases, scientists at City of Hope decided to first tackle a related, yet relatively more simple, nervous system disorder called Alexander disease. And this week, the strategy paid off with newly published research in Cell Stem Cell, funded in part by CIRM, describing the development of a patient-derived stem cell model system that could help evaluate novel treatments for all of these neurodegenerative diseases.
An Alexander disease patient's stem cell-derived astrocytes (green) inhibits the growth of precursor cells that, in healthy patients, becomes myelin and speed up the brain's communication network. Credit: Yanhong Shi/City of Hope
The team generated astrocytes, a type of nervous system cell, using induced pluripotent stem cells derived from Alexander disease patients. It was previously known that the mutation in Alexander disease causes the patient’s astrocytes to block another cell type’s ability to produce myelin, the protective covering over neurons that’s critical for communication between nerve cells. But it wasn’t clear how this inhibition happened. In this study, the team found a possible culprit, a protein called CHI3L1 that’s secreted by the patient-derived astrocytes (but not by those from healthy individuals) and interferes with myelin production. So, finding drugs that target CHI3L1 could lead to therapies for Alexander disease.
Dysfunctional astrocytes have also been implicated in ALS and Alzheimer’s disease. So, using this newly developed model system for studying astrocytes could lead to new therapeutic strategies. In a press release, team leader Dr. Yanhong Shi, PhD, provides a specific example how this could work:
“The bulk of ApoE4 resides in astrocytes; ApoE4 is a gene variant known for increasing the risk of Alzheimer’s disease. So, if we understand how astrocytes function, then we can develop therapies to treat Alexander disease and perhaps other diseases that involve astrocytes, such as Alzheimer’s and ALS.”